Endovascular photodynamic therapy with aminolaevulinic acid prevents balloon induced intimal hyperplasia and
E E E Gabeler1, R van Hillegersberg, R G Statius van Eps
1Department of Surgery, University Hospital Rotterdam-Dijkzigt, Erasmus MC, Room H928, Dr Molewaterplein 40, 3015 GE Rotterdam, The Netherlands.
Background And Objective:
intimal hyperplasia (IH) and constrictive remodelling are important causes of restenosis following endovascular interventions, such as percutaneous transluminal angioplasty. Photodynamic therapy (PDT) with 5-aminolaevulinic (ALA) may prevent restenosis by cellular depletion and the elimination of cholinergic innervation.
Study Design/Materials And Methods:
rats (n=90) were subdivided into 4 main groups. In the experimental group (n=36: 3 replications x 4 doses x 3 examination time-points), ALA was administered (200mg/kg i.v.) 2-3h before balloon injury (BI) of the common iliac artery followed by endovascular illumination with 633nm at either 12.5, 25, 50 or 100J/cm diffuser length (dl BI+PDT group). As control groups served the BI+Light only (LO) group (n=36) that received no ALA, the BI only group (n=9) (BI), and a group (n=9) that received a Sham procedure (Sham group).
Results:
planimetric analysis showed IH of 0.28+/-0.12mm(2) (BI), 0.27+/-0.12mm(2) (BI+LO at 100J/cmdl) in contrast to 0.02+/-0.02mm(2) after BI+PDT at 100J/cmdl at 16 weeks (p<0.05). In the BI+PDT groups, a light-dose increase of a factor 2 led to an IH decrease of 17% (p<0.05). In the BI and BI+LO groups constrictive remodelling was found, in contrast to BI+PDT treated groups at 16 weeks. The staining of cholinergic innervation of the tunic media of the blood vessel wall in BI+PDT showed no damage at the highest fluence.
Conclusion:
endovascular ALA-PDT prevents IH and constrictive remodelling after BI without damage of cholinergic innervation of the tunica media. The effective light fluence rate in the rat is 50-100J/cmdl.
